168
1. Analyze the obtained calorimetric data by using the software
installed in the thermometer.
2. Normalize each analysis per total sample weight (see Note 11).
3. Choose the desired thermodynamic parameters for each thermodynamic phenomenon, i.e. endothermic or exothermic.
These are the characteristic transition temperatures T onset and T,
enthalpy change ΔH, and width at half peak height of the C p
profiles ΔT 1/2 (see Note 12).
4. During peak integration, manually set the baseline (see Notes
13–15).
The profiles of all samples containing 2-HP-β-CD and irbesartan
or losartan are presented in Fig. 3.
The following observations can be made on the
thermograms:
∙ 2-HP-β-CD and its lyophilized form exhibited a melting transition at around 170 °C, with the first being more crystalline
than the second, resulting in a sharper peak and slightly higher
transition enthalpy (Fig. 3a, b) [12]. The two drugs gave transition peaks at around 185 °C and 270 °C for irbesartan and
losartan, respectively, with these values being very close to the
bibliography (Fig. 3c, d). In addition, a pre-transition was
recorded for losartan [14, 16, 17]. The lyophilized form of
losartan led to the appearance of another form of the molecule
that melts at 165 °C (Fig. 3e).
∙ The nature of the raw material physical mixture between
2-HP-β-CD and losartan was very different from that with
irbesartan (Fig. 3f, g). Though the molar ratio of
cyclodextrin:sartan was the same in the two cases (3.6:1), the
mixture with losartan led to an endothermic peak at 175 °C,
suggesting the existence of crystalline cyclodextrin in the mixture and the loss of crystallinity of losartan, due to intermolecular interactions. On the contrary, for irbesartan, there was
a low enthalpy peak at 170 °C and another at 200 °C, the first
owed to the cyclodextrin and the second to the drug, which
suggests that part of the drug has not been complexed and
only a small amount of cyclodextrin is in the crystalline state.
∙ The physical mixture of the drugs with lyophilized 2-HP-β-CD
led to similar profiles, where a small peak was observed for
irbesartan at 180 °C and for losartan at 240 °C. For losartan,
this should be attributed to the drug; however, in the case of
irbesartan, it could be due to the cyclodextrin, since the melting peaks of the two are very close.
∙ The complex of 2-HP-β-CD with irbesartan or losartan
resulted in different DSC heating profiles. For the first com3.5 DSC Diagram
and Thermodynamic
Parameter Extraction
3.6 DSC Profile
Analysis of the
Cyclodextrin:Sartan
Systems
Nikolaos Naziris et al.
1. Analyze the obtained calorimetric data by using the software
installed in the thermometer.
2. Normalize each analysis per total sample weight (see Note 11).
3. Choose the desired thermodynamic parameters for each thermodynamic phenomenon, i.e. endothermic or exothermic.
These are the characteristic transition temperatures T onset and T,
enthalpy change ΔH, and width at half peak height of the C p
profiles ΔT 1/2 (see Note 12).
4. During peak integration, manually set the baseline (see Notes
13–15).
The profiles of all samples containing 2-HP-β-CD and irbesartan
or losartan are presented in Fig. 3.
The following observations can be made on the
thermograms:
∙ 2-HP-β-CD and its lyophilized form exhibited a melting transition at around 170 °C, with the first being more crystalline
than the second, resulting in a sharper peak and slightly higher
transition enthalpy (Fig. 3a, b) [12]. The two drugs gave transition peaks at around 185 °C and 270 °C for irbesartan and
losartan, respectively, with these values being very close to the
bibliography (Fig. 3c, d). In addition, a pre-transition was
recorded for losartan [14, 16, 17]. The lyophilized form of
losartan led to the appearance of another form of the molecule
that melts at 165 °C (Fig. 3e).
∙ The nature of the raw material physical mixture between
2-HP-β-CD and losartan was very different from that with
irbesartan (Fig. 3f, g). Though the molar ratio of
cyclodextrin:sartan was the same in the two cases (3.6:1), the
mixture with losartan led to an endothermic peak at 175 °C,
suggesting the existence of crystalline cyclodextrin in the mixture and the loss of crystallinity of losartan, due to intermolecular interactions. On the contrary, for irbesartan, there was
a low enthalpy peak at 170 °C and another at 200 °C, the first
owed to the cyclodextrin and the second to the drug, which
suggests that part of the drug has not been complexed and
only a small amount of cyclodextrin is in the crystalline state.
∙ The physical mixture of the drugs with lyophilized 2-HP-β-CD
led to similar profiles, where a small peak was observed for
irbesartan at 180 °C and for losartan at 240 °C. For losartan,
this should be attributed to the drug; however, in the case of
irbesartan, it could be due to the cyclodextrin, since the melting peaks of the two are very close.
∙ The complex of 2-HP-β-CD with irbesartan or losartan
resulted in different DSC heating profiles. For the first com3.5 DSC Diagram
and Thermodynamic
Parameter Extraction
3.6 DSC Profile
Analysis of the
Cyclodextrin:Sartan
Systems
Nikolaos Naziris et al.